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Aging Cell. 2016 Feb;15(1):149-54. doi: 10.1111/acel.12421. Epub 2015 Nov 17.

DNA methylation age is associated with mortality in a longitudinal Danish twin study.

Author information

1
The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
2
Max Planck Odense Center on the Biodemography of Aging, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
3
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
4
Max Planck Institute for Demographic Research, Rostock, Germany.
5
The Center for Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
6
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
7
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.

Abstract

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging.

KEYWORDS:

DNA methylation; biological age; biomarker; epigenetic clock; mortality; twins

PMID:
26594032
PMCID:
PMC4717264
DOI:
10.1111/acel.12421
[Indexed for MEDLINE]
Free PMC Article

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